The in vivo efficacy of known inhibitors of rhinovirus replication may not correspond well with their in vitro activity. Al-Nakib et al. have reported in the Archives of Virology 92, p. 255-260 (1987) that 4',6-dichloroflavan did not produce any consistent or significant reduction in clinical parameters of infection even though it has a marked antirhinoviral activity in tissue culture. However, the poor results obtained severely limit the usefulness of this apparently potent agent. Similarly, Al-Nakib et al. in Journal of Antimicrobial Chemotherapy 20, 887-892 (1987), report that the administration of the antiviral chalcone (RO 09-0410) did not reduce the incidence of infection or illness in vivo.
The need in the art for effective in vivo delivery of potent in vitro rhinovirus inhibitors is further shown by F. G. Hayden in Antimicrobial Agents and Chemotherapy, June 1982, p. 892-897. In this article, in vivo results of intranasal administration of enviroxime are disclosed as being no better than placebo even though concentrations of the drug were at least 50 times higher than the in vitro inhibitory concentrations.
Similarly, in vivo test results for the synthetic rhinovirus specific antiviral RMI-15,731 from Merrell Dow Pharmaceuticals were reported in Abstract 931 at the 23rd Interscience Con. Antimicrobial Agents Chemotherapy in Las Vegas, U.S.A., in October 1983. The clinical results showed that RMI-15,731 did not show significant prophylactic activity as compared to placebo.
The failure of agents active in vitro to prove out in vivo is particularly frustrating since high concentrations of the agents are found over the test period in the area of infection.